There is enough evidence that sex hormones may influence promoting phase of hepatocarcinogenesis apart from their effect upon initiation which operates through enzyme system activating chemical carcinogens. Clinical and experimental data show that males develop liver tumors more readily than females. Also, change in hormonal environment triggered by gonadectomy or administration of sex hormones following initiation modifies incidence of liver tumors, indicating strongly its modulating effect upon promotion of neoplastic process. Recent clinical observations suggest that use of oral contraceptives and anabolic steroids may be causally related to observed increase in the incidences of focal nodular lesions and even hepatocellular carcinomas in individuals using such hormones for long periods. The hypothesis that synthetic hormones may also achieve their effect by influencing promotion could be tested and defined in a system developed in our laboratory, in which single low dose levels of diethylnitrosamine (DEN) (less than or equal to 0.15 micrograms/g body weight) were shown to be effective in initiating hepatocarcinogensis in C57BLxC3H F1 mice. Slightly higher, but still low, dose levels (0.6 to 5.0 micrograms/g body weight) were able to induce nodular liver lesions, ranging from hyperplastic to adenomatous and malignant cell populations, their incidence depending upon the dose of carcinogen used and the length of observation period. In the proposed study, promoting effect of norethynodrel, mestranol, methyltestosterone, and oxymetholone will be tested in groups of mice conditioned by subeffective (initiating) and marginally carcinogenic (inducing) single dose treatments of DEN by assessing type and incidence of developing lesions. Possible weak carcinogenic activity of the above hormones will be concurrently assessed. Phenobarbitone (0.05%) will be used as positive promoter.